Human Physiology, 14th edition (2016)

690 Chapter 19

elevation in blood Ca^2 1 by stimulating resorption of the cal-

cium phosphate crystals from bone and renal excretion of

phosphate. 1,25-dihydroxyvitamin D 3 promotes the intesti-

nal absorption of calcium and phosphate.

| CHECKPOINT

12a. Describe the effects of epinephrine and the

glucocorticoids on the metabolism of carbohydrates

and lipids. What is the significance of these effects

as a response to stress?

12b. Explain the actions of thyroxine on the basal

metabolic rate. Why do people with hypothyroidism

have a tendency to gain weight, and why are they

less resistant to cold stress?

13a. Describe the effects of growth hormone on the

metabolism of lipids, glucose, and amino acids.

13b. Explain how growth hormone stimulates skeletal

growth.

19.6 REGULATION OF CALCIUM

AND PHOSPHATE BALANCE

A normal blood Ca^2 1 concentration is critically important for

contraction of muscles and maintenance of proper mem-

brane permeability. Parathyroid hormone promotes an

LEARNING OUTCOMES

After studying this section, you should be able to:

14. Describe the hormonal regulation of blood calcium
    and how this affects the skeletal system.


15. Explain how 1,25-dihydroxyvitamin D 3 is formed and
    describe its actions.

CLINICAL APPLICATION

Recombinant human growth hormone has replaced the

previously limited amount of growth hormone that was derived

from the pituitary glands of cadavers in the medical treatment

of pituitary dwarfism. In 2003 the FDA also approved the use

of recombinant human growth hormone to treat children with

idiopathic (of unknown cause) short stature if they are below

the first percentile. This requires weekly injections during the

growing years. Such treatment has been found to increase

their eventual adult height by 1.2 to 2.8 inches (3.0 to 7.1 cm).

Although the immediate risks to health are low, there is a

possibility of increased risk for serious diseases later in life.

Because of this, medical scientists have recommended that

human growth hormone be used conservatively for the treat-

ment of idiopathic short stature.

The calcium and phosphate concentrations of plasma are affected

by bone formation and resorption, intestinal absorption of Ca^2 1

and PO 4 3 2 , and urinary excretion of these ions. These processes

are regulated by parathyroid hormone, 1,25-dihydroxyvitamin D 3 ,

and calcitonin, as summarized in table 19.6.

Bone Deposition and Resorption

The skeleton, in addition to providing support for the body, serves

as a large store of calcium and phosphate in the form of crystals

called hydroxyapatite, which has the formula Ca 10 (PO 4 ) 6 (OH) 2.

The calcium phosphate in these hydroxyapatite crystals is

derived from the blood by the action of bone-forming cells, or

osteoblasts. The osteoblasts secrete an organic matrix composed

largely of collagen protein, which becomes hardened by deposits

of hydroxyapatite. This process is called bone deposition. Bone

resorption (dissolution of hydroxyapatite), produced by the

action of osteoclasts ( fig.  19.18 a ), results in the return of bone

calcium and phosphate to the blood.

Osteoclasts are macrophage-like cells, and their develop-

ment requires stimulation by macrophage-colony stimulating

factor ( M - CSF ). Under stimulation by M-CSF, osteoclast pro-

genitor cells produce a receptor protein known by its acronym

RANK. These cells are then stimulated to develop into osteo-

clasts by RANK ligand ( RANKL ), which is secreted by osteo-

cytes and other cells. This is a highly regulated process, and

osteocytes may also secrete osteoprotegerin, a molecule that

blocks RANKL from binding to RANK.

Table 19.6 | Endocrine Regulation of Calcium and Phosphate Balance

Hormone

Effect on

Intestine Effect on Kidneys Effect on Bone Associated Diseases

Parathyroid hormone (PTH) No direct effect Stimulates Ca^21

reabsorption; inhibits

PO 432 reabsorption

Stimulates resorption Osteitis fibrosa cystica with

hypercalcemia due to excess

PTH

1,25-dihydroxyvitamin D 3 Stimulates

absorption of

Ca^21 and PO 432

Stimulates reabsorption of

Ca^21 and PO 432

Stimulates resorption Osteomalacia (adults) and rickets

(children) due to deficiency of

1,25-dihydroxyvitamin D 3

Calcitonin None Inhibits resorption of Ca^21

and PO 432

Stimulates deposition None